This Notice reminds the grantee community of the principles and requirements of the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines). Recombinant DNA is a critically important tool used widely in many lines of biological research. While it has been in use for over 30 years, it continues to raise many important scientific, ethical, and safety considerations. These considerations are of special concern when recombinant DNA research involves highly pathogenic organisms or the participation of human research subjects, where potential risks to individuals and the environment are greater.

The NIH Guidelines were developed to help the scientific community manage these risks responsibly. They stipulate biosafety and containment measures for recombinant DNA research that serve to protect laboratory workers, our communities, and the environment. Furthermore, they outline essential ethical principles and key safety reporting requirements for human gene transfer research.

Investigators and institutions are reminded that they must adhere to the NIH Guidelines when they perform research involving recombinant DNA molecules that is conducted at, or sponsored by, an entity receiving any NIH support for recombinant DNA research. Therefore, even privately funded projects employing recombinant DNA must adhere to the NIH Guidelines if they are being carried out at, or funded by, an organization that has any NIH contracts, grants, or other support for this kind of research. A fully indexed and easily navigated version of the NIH Guidelines can be accessed at: http://www4.od.nih.gov/oba/rac/guidelines/guidelines.html

Institutional Biosafety Committees - Institutions subject to the NIH Guidelines are required to establish and maintain an Institutional Biosafety Committee (IBC) for the review of recombinant DNA research, including registering the IBC with the NIH Office of Biotechnology Activities (OBA). Furthermore, updated information on the IBC’s membership must be filed annually with OBA. Unless exempt from the NIH Guidelines, experiments involving recombinant DNA must at a minimum be registered with the IBC, and certain types of experiments require IBC review and approval prior to initiation. IBCs are also responsible for ensuring that experiments requiring NIH input, NIH Recombinant DNA Advisory Committee (RAC) review, or NIH approval are appropriately registered with the NIH and not initiated until the NIH review process is complete. Such experiments include human gene transfer trials (see below) and certain genetic modifications of microorganisms that confer antibiotic resistance traits or result in the product of especially potent toxins. IBCs must also ensure that significant research-related accidents or violations of the NIH Guidelines are promptly reported to OBA. More information on these requirements can be found at: http://www4.od.nih.gov/oba/IBC/IBCindexpg.htm

Requirements for human gene transfer trials - Investigators conducting human gene transfer research at, or sponsored by, an institution that receives NIH support for recombinant DNA research must comply with Appendix M of the NIH Guidelines. Appendix M outlines points to consider in the design and submission of these protocols to OBA. Under Appendix M, investigators conducting trials subject to the NIH Guidelines must register their protocols with OBA and provide certain information about the trials for review by the NIH and, possibly, the NIH Recombinant DNA Advisory Committee. Once a trial is initiated, further information is to be submitted to NIH, including reports of serious adverse events (SAEs). More information about Appendix M requirements can be found in “Frequently Asked Questions” at: http://www4.od.nih.gov/oba/RAC/RAC_FAQs.htm

Investigators are encouraged to report adverse events using the NIH Genetic Modification Clinical Research Information System (GeMCRIS). This system provides an online reporting format enabling the creation of reports that can be submitted electronically to the NIH and that can be conveyed to the FDA and the institutional oversight committees that may need to review them (see below). More about using GeMCRIS for on- line reporting can be found at: http://www4.od.nih.gov/oba/RAC/GeMCRIS/GeMCRIS.htm

Inquiries

It is critically important that institutions and their investigators adhere to the NIH Guidelines. Investigators and administrators are encouraged to contact OBA with any questions they may have concerning these and other requirements. Questions can be directed to: